Sickle cell anemia, the most common genetic disorder worldwide, causes hemoglobin in red blood cells to crystallize. This leads to rigid, sickle-shaped cells that can block blood flow and result in serious complications such as circulatory problems, organ failure, and reduced life expectancy. The disease is particularly severe for children and adolescents.
Current treatments include hydroxyurea, which can improve quality of life but is not suitable for all patients due to tolerability issues. Bone marrow transplants are another option but are limited by donor availability. Other therapies like gene therapy or therapeutic antibodies remain prohibitively expensive.
An international research team led by Max Gassmann, professor emeritus of veterinary physiology at the University of Zurich, is exploring a more affordable alternative: repurposing memantine, a drug used for Alzheimer's disease for about two decades and no longer under patent protection. Previous preclinical studies showed that memantine could stabilize red blood cells.
"In the best case, memantine would be available for the treatment of sickle cell anemia, as a well-tolerated, easy-to-store, and very cost-effective drug that is no longer patent-protected," said Max Gassmann. He noted this could be especially important in regions with high rates of sickle cell anemia and limited resources such as Africa or parts of India.
A phase II study involved 17 participants who received age-appropriate doses of memantine over 12 months. Researchers found the treatment was well tolerated and confirmed its safety through more than 25 laboratory parameters over two to three years. The study also showed clear clinical benefits: both the number and duration of hospitalizations decreased significantly. Children experienced fewer painful episodes related to their condition. No serious side effects or discontinuations were reported due to the therapy itself.
All participants continued their existing hydroxyurea therapy during the study because stopping it would have been unethical. "The observed effects should therefore be interpreted as complementary to hydroxyurea," Gassmann explained.
The research team plans a follow-up study including patients who have not previously received hydroxyurea in order to systematically analyze combination therapies and further evaluate memantine’s clinical efficacy.
